Canagliflozin (I) is a SGLT-2 inhibitor used for the treatment of diabetes (Chao, E.C. Drugs Fut. 2011, 36(5), 351) acting by blocking the re-absorption of glucose in the kidneys and its excretion in the urine.
The selection of a suitable polymorphic form of the active substance is very important because it influences its solubility, chemical stability, purification effect during isolation, mechanical properties as the particle size etc., which are important during the preparation of drug forms.
Therefore, new forms of Canagliflozin are still being looked for and discovered with the aim to control solubility, chemical stability, purification effect during crystallization or to ensure suitable mechanical properties.
The patent of the company Mitsubishi Tanabe WO2008069327A1 describes and claims a crystalline form of canagliflozin hydrate and a process of its preparation. This polymorph is characterized by the XRPD 2θ CuKα diffraction peaks: 4.36, 13.54, 16.00, 19.32, 20.80
The following patent of the companies Janssen and Mitsubishi WO2009035969A1 describes preparation of the crystalline hydrate I-S and also claims a tetraacetyl derivative of canagliflozin. There, the form I-S is characterized by the following XRPD 2θ CuKα diffraction peaks: 3.9 8.0 9.7 10.9 13.0 13.9 15.5 15.6 15.9 16.2 17.3 18.3 18.7 18.8 19.1 19.4 20.3 20.9 21.1 21.8 22.5 22.7 23.2 23.4 25.1 25.7 26.3 26.8
Further, cocrystals of canagliflozin with L-proline and citric acid have been described (WO-2012154812, Janssen Pharmaceutica).
The patent application WO 2013064909 of the company SCINOPHARM claims five crystalline complexes and an amorphous form of Canagliflozin. Namely: Form CS1—complex with L-proline (1:1), form CS-2—complex with D-proline (1:1), form CS-3—complex with L-phenylalanine (1:1), form CS4—complex with D-proline (1:1) obtained by heating (125° C.) of form CS-2 or another complex with D-proline (1:1) and form CS-5 obtained by heating of form CS-4.
The patent application WO2014180872 of the company LEK PHARMACEUTICALS describes and claims non-stoichiometric hydrates of Canagliflozin prepared by suspending of the API in water and drying in an environment with controlled humidity. Form HxA, characterized by the XRPD 2θ CuKα diffraction peaks: 5.4±0.2°, 6.7±0.2°, 13.2±0.2°, 16.1 ±0.2°, 19.6±0.2° and
form HxB, which is characterized by the XRPD 2θ CuKα diffraction peaks: 6.6±0.2°, 7.3±0.2°, 12.2±0.2°, 15.4±0.2°, 19.9±0.2°.
The application WO 2015071761 of the company CRYSTAL PHARMATECH describes and claims three crystalline forms referred to as B, C, D. Form B is characterized by the XRPD 2θ CuKα diffraction peaks: 6.3 9.4 11.7 12.6 16.9 18.2 19.9 22.3 24.4 28.9. Form C is characterized by the XRPD 2θ CuKα diffraction peaks: 6.5, 9.8, 13.4, 16.4, 17.1, 19.5, 19.8, 23.7 25.2 26.5 and finally form D is characterized by the XRPD 2θ CuKα diffraction peaks: 6.8 10.2 13.6 16.5 17.1 18.5 19.2 20.5 22.9 24.4.
The application CN 103641822A of the company Faming Zhuanli Shenqing describes a form characterized by the XRPD 2θ CuKα diffraction peaks: 3.86, 15.46, 17.30, 18.80, 19.10 and 20.26, which however seems to be identical to the form from the patent WO2009035969 according to XRPD.
Another application CN 103980261 A of UNIVERSITY TIANJIN; QILU describes the crystalline form A and its preparation. Form A is characterized by the XRPD 2θ CuKα diffraction peaks: 3.7, 3.9, 7.7, 7.9, 11.5, 13.1, 13.5, 14.3, 15.5, 17.3, 18.8, 19.3, 20.3, 22.5, 22.7, 23.2 and 23.4.
Preparation of an eutectic mixture of Canagliflozin and L-phenylalanine is described by the application CN 103965267 AO (priority CN2013128068 20130124) of the company JIANGSU HANSOH PHARMACEUTICAL.
The application CN 103936725 A (20140723) of Faming (priority CN20141129127 20140401) describes form C and a method of its preparation. Form C is characterized by the XRPD 2θ CuKα diffraction peaks: 3.4, 6.5, 12.7, 15.8, 19.8, 24.3, 24.8 and 29.1.
The patent application CN 103936726 A (priority CN20141155712 20140418) of the company SUZHOU JINRAN PHARMACEUTICAL TECHNOLOGY CO LTD describes and claims crystalline forms III and IV and methods of their preparation. Form III—complex with octanol is characterized by the XRPD 2θ CuKα diffraction peaks: 6.61, 3.92 and 19.68 and form IV—an anhydrate prepared by washing of form III with n-heptane, filtering and drying under reduced pressure is characterized by the XRPD 2θ CuKα diffraction peaks: 17.40, 15.35 and 14.91.
The patent application CN104119323 (A) of the company CHONGQING PHARM RES INST CO describes and claims an amorphous form and a process of its preparation. The amorphous form is characterized by a DSC (Differential Scanning Calorimetry) endothermic peak in the temperature range of 53-63° C. and has characteristic absorption peaks at the wavelengths of approx. 832 cm−1 and 809cm−1 in the infrared spectrum.
The patent application CN 104230907 A of the company Faming Zhuanli Shenqing describes and claims a crystalline form and its use.
The patent application WO2014195966 (A2) of the company Cadila describes and claims a stable amorphous form and a process of its preparation and a solid solution of this API and a process of its preparation. Specific polymers for the preparation of solid solutions are mentioned (HPMC-AS, HPMC, copolymers of methacrylic acid, PVP).
Another patent application of the company Zentiva CZ PV 2014-634 describes and claims complexes of canagliflozin and cyclodextrins and methods of their preparation. These complexes can be advantageously used for stabilization of amorphous canagliflozin from the chemical and polymorphic stability point of view. β-cyclodextrin, modified β-cyclodextrins and γ-cyclodextrin were mainly used for the complexation of canagliflozin.